Lymphoblastic LeukemiaLALPh2022NCT06175702
Treatment Protocol for Newky Diagnosed Adult Ph Positive ALL
An observational study of Lymphoblastic Leukemia and Philadelphia-Positive ALL, run by PETHEMA Foundation.
Trial summary
The goal of this prospective, multicenter, open observational study is to assess the efficacy and safety of the treatment for acute lymphoblastic leukemia Ph' positive adult patients with approved combinations of chemotherapy and tyrosine kinase inhibitor (TKI). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoblastic Leukemia, Philadelphia-Positive ALL, Adult ALL
- What is being tested?
- Vincristine, Dexamethasone and Imatinib
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 150 participants
- Where
- No sites listed yet
- Study dates
- 25 Dec 2023to 25 Dec 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adults aged 18 or over years with newly diagnosed Ph-positive or BCR::ABL1-positive acute lymphoblastic leukemia (Ph+ ALL).
Who may be able to join
- Patients with de novo avute lymphoblastic leukeima (ALL) Philadelphia chromosome-positive (BCR::ABL1) aged ≥18 years.
- CML blast crisis will be included. These patients will always receive transplantation, regardless of the molecular response or the genetic risk, following the recommendations of the SEHH CML group (Chronic Myleoid Leukemia Group from the Spanish Society of Hematology).
- Performance status 0-2; patients with performance status>2 attributable to ALL can be included.
- Patients without functional alteration of organs; liver function: total bilirubin, GOT, GPT, GGT and alkaline phosphatase less than 3 times the upper limit of the normal range of the laboratory; renal function: serum creatinine <2 mg/dl or creatinine clearance > 30 ml/min (except altered renal function attributable to ALL); normal heart function: EF ventricular > 50%; absence of severe chronic respiratory disease. In case that the alterations are secondary to the disease, it is at the discretion of the physician to determine if the patient can be included in the study.
Who cannot join
- Any other subtype of ALL.
- Patients with chronic liver disease.
- Patients with chronic respiratory failure.
- Renal failure not due to ALL.
- Lipase and amylase>1.5× ULN.
- Patients with positive HIV serology.
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- Serious neurological alterations not due to ALL.
- Serious general condition condition (grades 3 or 4 on the WHO scale) not attributable to ALL.
- Pregnant or breastfeeding women.
- Impaired cardiac function (defined by an ejection fraction less than 50%), any clinically significant active or uncontrolled cardiovascular condition, uncontrolled hypertension, arrhythmias, ischemic cardiovascular or neurological events, deep vein thrombosis, pulmonary thromboembolism, history of acute pancreatitis in the year before diagnosis of ALL or history of chronic pancreatitis and triglycerides >450 mg/dL.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Treatment Protocol for Newky Diagnosed Adult Ph-Chromosome Positive (BCR::ABL1) Acute Lymphoblastic Leukemia (LALPh2022)
The goal of this prospective, multicenter, open observational study is to assess the efficacy and safety of the treatment for acute lymphoblastic leukemia Ph' positive adult patients with approved combinations of chemotherapy and tyrosine kinase inhibitor (TKI).
Efficay refers to the rate of Complete Molecular Response (BCR::ABL1/ABL1 ratio 0.01%) in eah treatment arm. Safety refers to measurement of i) Adverse events (AEs) and serious adverse events (SAEs) according to standard clinical and laboratory tests (hematology and chemistry, physical examination, vital sign measurements, and diagnostic tests), ii) incidence and degree of cytopenias and iii) incidence and degree of infections.
Read more
Low-dose chemotherapy will be given together with the TKI imatinib to patients of all ages as induction to remission phase.
Consolidation treatment will continue with low-dose chemotherapy with imatinib if the patient fullfills both criteria: to show a measurable residual disease (MRD) value lower than 0,01% at 3 month of therapy, and not showing IKZF1plus genetics Those patients have any of these 2 conditions will be considered high-risk patients and will recieve consolidation treatment intensification with low-dose chemotherapy plus ponatinib as TKI and allogeneic stem cell transplantation (allo SCT). The remaining patients (standard-risk) will receive maintenance chemotherapy together with imatinib or ponatinib and will not be submitted to alloSCT.
Read the detailed description
The goal of this prospective, multicenter, open observational study is to assess the efficacy and safety of the treatment for acute lymphoblastic leukemia Ph' positive adult patients with approved combinations of chemotherapy and tyrosine kinase inhibitor (TKI).
Efficay refers to the rate of Complete Molecular Response (BCR::ABL1/ABL1 ratio 0.01%) in each treatment arm. Safety refers to measurement of i) Adverse events (AEs) and serious adverse events (SAEs) according to standard clinical and laboratory tests (hematology and chemistry, physical examination, vital sign measurements, and diagnostic tests), ii) incidence and degree of cytopenias and iii) incidence and degree of infections.
Low-dose chemotherapy induction phase with vincristine (dose 1.5 mg/m2 at days 1, 8, 15 and 22), dexamethasone (dose 40 mg days 1-2, 8-9,15-16 and 22-23) will be given together with the TKI imatinib (dose 600 mg from day to consolidation start) to all patients of all ages as induction to remission phase.
Consolidation treatment will continue with low-dose chemotherapy with methotrexate (dose 1000 mg/m2 on day 1 with 24h infusion) and arabinoside of cytarabine (dose 1000 mg/m2/ days 1, 3 and 5 with 2h infusion) with imatinib (dose 600 mg per day) if the patient fullfills both criteria: i) to show a measurable residual disease (MRD) value <0,01% at 3 month of therapy, and ii) not showing IKZF1plus genetics.
Those patients having any of these 2 conditions will be considered high-risk patients and will recieve consolidation treatment intensification with low-dose chemotherapy (same as described above) plus ponatinib (dose 30 mg per day) as TKI and allogeneic stem cell transplantation (alloSCT) followed by maintenance chemotherapy with mercaptopurine (dose 50 mg/m2 on days 1 to 28) and methotrexate (dose 20 mg/m2 on days 1, 8, 15 and 22) together with imatinib (dose 600 mg per day) or ponatinib (15 mg per day) up to 5 years. The remaining patients (standard-risk) will receive maintenance chemotherapy (as described above) together with imatinib (dose 600 mg per day) or ponatinib (15 mg per day) up to 5 years and will not be submitted to alloSCT.
- Conditions
- Lymphoblastic Leukemia, Philadelphia-Positive ALL, Adult ALL
- Being tested
- Vincristine, Dexamethasone, Imatinib, Cytarabine, Mercaptopurine
- Keywords
- Acute Lymphoblastic Leukemia, Philadelphia (BCR::ABL1) positive, Adults
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VincristineDrug
dose 1.5 mg/m2 at days 1, 8, 15 and 22
DexamethasoneDrug
40 mg on days 1-2, 8-9,15-16 and 22-23
ImatinibDrug
600 mg per day from 1 to up to 5 years
CytarabineDrug
1000 mg/m2/ on days 1, 3 and 5 of consolidation with 2h infusion
MercaptopurineDrug
50 mg/m2 on days 1 to 28 of maintenance
MethotrexateDrug
1000 mg/m2 on day 1 of consolidation with 24h infusion; and 20 mg/m2 on days 1, 8, 15 and 22 of maintenance
PonatinibDrug
15 mg per day from consolidation start up to 5 years
allogeneic stem cell transplantationProcedure or surgery
Allogeneic stem cell transplantation from hematpoietic stem cells progenitors of familiar or not familiar origin. Cord blood transplantation can also be done.
Total body irradiationProcedure or surgery
Fractionated dose with total dose of 12 Gy between days -4 and -1 of allogeneic stem cell transplantation (alloSCT)
CyclophosphamideDrug
60 mg/kg on days -6 and -5 before alloSCT
FludarabineDrug
30 mg/m2 intravenous on days -7, -6, -5 y -4 before alloSCT (alternative to cyclophosphamide)
| Study group | Role | What they receive |
|---|---|---|
| Complete molecular response and low risk genetics | Patients in Complete Remission and Complete Molecular Response at end Induction therapy will receive consolidation with imatinib (or dasatinib if intolerance) and chemotherapy, unless they show the IKZF1plus genotype, which will imply switch to the not complete molecular response or high-risk genetics (IKZ1plus) group. Receives: Drug: Vincristine; Drug: Dexamethasone; Drug: Imatinib; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Methotrexate | |
| Not complete molecular response or high-risk genetics (IKZF1plus) | Patients in Complete Remission and without Complete Molecular Response at the end of Induction therapy or showing the IKZF1plus genotype, will receive consolidation treatment with ponatinib and chemotherapy followed by allogeneic stem cell transplantation and maintenance therapy. Receives: Drug: Vincristine; Drug: Dexamethasone; Drug: Imatinib; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Ponatinib; Procedure: allogeneic stem cell transplantation; Procedure: Total body irradiation; Drug: Cyclophosphamide; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
Improvement of OS compared to that observed in the previous protocols (PETHEMA LALPh08 and LALOPh07).
Measured: 5 Years
Secondary outcomes (5)
Change the complete molecular response (CMR) rate with Ponatinib
Change the CMR rate at the end of consolidation with the administration of ponatinib to those patients who do not achieve CMR at the end of induction or have high-risk genetics (IKZF1plus).
Measured: 5 Years
Limit the number of alloTPH compared to that observed in the previous protocols (PETHEMA LALPh08 and LALOPh07).
Limit the number of alloTPH to any of the following:
- Lack of CMR at the end of consolidation.
- High-risk genetics (IKZF1plus).
Measured: 5 Years
Maintenance
To assess the number of non-transplanted participants who receive maintenance treatment.
Measured: 5 Years
Treatment with TKI after HSCT
To assess the number of transplanted patients who receive TKI maintenance treatment preemptively (upon of MRD>0.01%).
Measured: 5 Years
Assess the frequency and degree of Adverse Events
Assess the frequency of cytopenias and degree. Assess the frequency of infections and degree. Assess the frequency of vascuar events and degree. Assess the frequency of hepatic events and degree. Assess the frequency of pancreatic events and degree.
Measured: 5 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2023
- Study start25 Dec 2023 (estimated)
- Primary completion25 Dec 2028 (estimated)
- Study completion25 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (33)Papers the sponsor has linked to this study.
- Other trials for Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- PETHEMA Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Josep M Ribera Santasusana, MD, Principal investigator, Institut Catala d'Oncologia-Hospital Universitari Germans Trias i Pujol
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06175702
- Sponsor's protocol ID
- PETHEMA LALPh2022
- Acronym
- LALPh2022
- Status last verified
- Nov 2023
- First submitted
- 17 Nov 2023
- Last updated
- 19 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chiaretti S, Vitale A, Cazzaniga G, Orlando SM, Silvestri D, Fazi P, Valsecchi MG, Elia L, Testi AM, Mancini F, Conter V, te Kronnie G, Ferrara F, Di Raimondo F, Tedeschi A, Fioritoni G, Fabbiano F, Meloni G, Specchia G, Pizzolo G, Mandelli F, Guarini A, Basso G, Biondi A, Foa R. Clinico-biological features of 5202 patients with acute lymphoblastic leukemia enrolled in the Italian AIEOP and GIMEMA protocols and stratified in age cohorts. Haematologica. 2013 Nov;98(11):1702-10. doi: 10.3324/haematol.2012.080432. Epub 2013 May 28.
PubMed 23716539Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. doi: 10.1182/blood-2013-09-529008. Epub 2013 Nov 25.
PubMed 24277073Ribera JM, Oriol A, Gonzalez M, Vidriales B, Brunet S, Esteve J, Del Potro E, Rivas C, Moreno MJ, Tormo M, Martin-Reina V, Sarra J, Parody R, de Oteyza JP, Bureo E, Bernal MT; Programa Espanol de Tratamiento en Hematologia; Grupo Espanol de Trasplante Hemopoyetico Groups. Concurrent intensive chemotherapy and imatinib before and after stem cell transplantation in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Final results of the CSTIBES02 trial. Haematologica. 2010 Jan;95(1):87-95. doi: 10.3324/haematol.2009.011221. Epub 2009 Oct 1.
PubMed 19797728Daver N, Thomas D, Ravandi F, Cortes J, Garris R, Jabbour E, Garcia-Manero G, Borthakur G, Kadia T, Rytting M, Konopleva M, Kantarjian H, O'Brien S. Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica. 2015 May;100(5):653-61. doi: 10.3324/haematol.2014.118588. Epub 2015 Feb 14.
PubMed 25682595Chiaretti S, Vitale A, Vignetti M, Piciocchi A, Fazi P, Elia L, Falini B, Ronco F, Ferrara F, De Fabritiis P, Luppi M, La Nasa G, Tedeschi A, Califano C, Fanin R, Dore F, Mandelli F, Meloni G, Foa R. A sequential approach with imatinib, chemotherapy and transplant for adult Ph+ acute lymphoblastic leukemia: final results of the GIMEMA LAL 0904 study. Haematologica. 2016 Dec;101(12):1544-1552. doi: 10.3324/haematol.2016.144535. Epub 2016 Aug 11.
PubMed 27515250Chalandon Y, Thomas X, Hayette S, Cayuela JM, Abbal C, Huguet F, Raffoux E, Leguay T, Rousselot P, Lepretre S, Escoffre-Barbe M, Maury S, Berthon C, Tavernier E, Lambert JF, Lafage-Pochitaloff M, Lheritier V, Chevret S, Ifrah N, Dombret H; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia. Blood. 2015 Jun 11;125(24):3711-9. doi: 10.1182/blood-2015-02-627935. Epub 2015 Apr 15.
PubMed 25878120Foa R, Vitale A, Vignetti M, Meloni G, Guarini A, De Propris MS, Elia L, Paoloni F, Fazi P, Cimino G, Nobile F, Ferrara F, Castagnola C, Sica S, Leoni P, Zuffa E, Fozza C, Luppi M, Candoni A, Iacobucci I, Soverini S, Mandelli F, Martinelli G, Baccarani M; GIMEMA Acute Leukemia Working Party. Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2011 Dec 15;118(25):6521-8. doi: 10.1182/blood-2011-05-351403. Epub 2011 Sep 19.
PubMed 21931113Ravandi F, Othus M, O'Brien SM, Forman SJ, Ha CS, Wong JYC, Tallman MS, Paietta E, Racevskis J, Uy GL, Horowitz M, Takebe N, Little R, Borate U, Kebriaei P, Kingsbury L, Kantarjian HM, Radich JP, Erba HP, Appelbaum FR. US Intergroup Study of Chemotherapy Plus Dasatinib and Allogeneic Stem Cell Transplant in Philadelphia Chromosome Positive ALL. Blood Adv. 2016 Dec 27;1(3):250-259. doi: 10.1182/bloodadvances.2016001495.
PubMed 29046900Sugiura I, Doki N, Hata T, Cho R, Ito T, Suehiro Y, Tanaka M, Kako S, Matsuda M, Yokoyama H, Ishikawa Y, Taniguchi Y, Hagihara M, Ozawa Y, Ueda Y, Hirano D, Sakura T, Tsuji M, Kamae T, Fujita H, Hiramoto N, Onoda M, Fujisawa S, Hatta Y, Dobashi N, Nishiwaki S, Atsuta Y, Kobayashi Y, Hayakawa F, Ohtake S, Naoe T, Miyazaki Y. Dasatinib-based 2-step induction for adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood Adv. 2022 Jan 25;6(2):624-636. doi: 10.1182/bloodadvances.2021004607.
PubMed 34516628Kim DY, Joo YD, Lim SN, Kim SD, Lee JH, Lee JH, Kim DH, Kim K, Jung CW, Kim I, Yoon SS, Park S, Ahn JS, Yang DH, Lee JJ, Lee HS, Kim YS, Mun YC, Kim H, Park JH, Moon JH, Sohn SK, Lee SM, Lee WS, Kim KH, Won JH, Hyun MS, Park J, Lee JH, Shin HJ, Chung JS, Lee H, Eom HS, Lee GW, Cho YU, Jang S, Park CJ, Chi HS, Lee KH; Adult Acute Lymphoblastic Leukemia Working Party of the Korean Society of Hematology. Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Blood. 2015 Aug 6;126(6):746-56. doi: 10.1182/blood-2015-03-636548. Epub 2015 Jun 11.
PubMed 26065651Jain N, Maiti A, Ravandi F, Konopleva M, Daver N, Kadia T, Pemmaraju N, Short N, Kebriaei P, Ning J, Cortes J, Jabbour E, Kantarjian H. Inotuzumab ozogamicin with bosutinib for relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia or lymphoid blast phase of chronic myeloid leukemia. Am J Hematol. 2021 Aug 1;96(8):1000-1007. doi: 10.1002/ajh.26238. Epub 2021 May 28.
PubMed 33991360Vignetti M, Fazi P, Cimino G, Martinelli G, Di Raimondo F, Ferrara F, Meloni G, Ambrosetti A, Quarta G, Pagano L, Rege-Cambrin G, Elia L, Bertieri R, Annino L, Foa R, Baccarani M, Mandelli F. Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive patients with acute lymphoblastic leukemia without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) LAL0201-B protocol. Blood. 2007 May 1;109(9):3676-8. doi: 10.1182/blood-2006-10-052746. Epub 2007 Jan 9.
PubMed 17213285Rousselot P, Coude MM, Gokbuget N, Gambacorti Passerini C, Hayette S, Cayuela JM, Huguet F, Leguay T, Chevallier P, Salanoubat C, Bonmati C, Alexis M, Hunault M, Glaisner S, Agape P, Berthou C, Jourdan E, Fernandes J, Sutton L, Banos A, Reman O, Lioure B, Thomas X, Ifrah N, Lafage-Pochitaloff M, Bornand A, Morisset L, Robin V, Pfeifer H, Delannoy A, Ribera J, Bassan R, Delord M, Hoelzer D, Dombret H, Ottmann OG; European Working Group on Adult ALL (EWALL) group. Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL. Blood. 2016 Aug 11;128(6):774-82. doi: 10.1182/blood-2016-02-700153. Epub 2016 Apr 27.
PubMed 27121472Short NJ, Jabbour E, Sasaki K, Patel K, O'Brien SM, Cortes JE, Garris R, Issa GC, Garcia-Manero G, Luthra R, Thomas D, Kantarjian H, Ravandi F. Impact of complete molecular response on survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2016 Jul 28;128(4):504-7. doi: 10.1182/blood-2016-03-707562. Epub 2016 May 27.
PubMed 27235138Sasaki K, Kantarjian HM, Short NJ, Samra B, Khoury JD, Kanagal Shamanna R, Konopleva M, Jain N, DiNardo CD, Khouri R, Garcia-Manero G, Kadia TM, Wierda WG, Khouri IF, Kebriaei P, Mehta RS, Champlin RE, Garris R, Cheung CM, Daver N, Thompson PA, Yilmaz M, Ravandi F, Jabbour E. Prognostic factors for progression in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia in complete molecular response within 3 months of therapy with tyrosine kinase inhibitors. Cancer. 2021 Aug 1;127(15):2648-2656. doi: 10.1002/cncr.33529. Epub 2021 Apr 1.
PubMed 33793964
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment Protocol for Newky Diagnosed Adult Ph-Chromosome Positive (BCR::ABL1) Acute Lymphoblastic Leukemia (LALPh2022)
- ClinicalTrials.gov ID
- NCT06175702
- Acronym / sponsor ID
- LALPh2022 / PETHEMA LALPh2022
- Conditions
- Lymphoblastic Leukemia, Philadelphia-Positive ALL, Adult ALL
- Keywords
- Acute Lymphoblastic Leukemia, Philadelphia (BCR::ABL1) positive, Adults
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- PETHEMA FoundationUniversity, hospital or other
- Study start
- 25 Dec 2023 (estimated)
- Primary completion
- 25 Dec 2028 (estimated)
- Study completion
- 25 Dec 2030 (estimated)
- First posted
- 19 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this prospective, multicenter, open observational study is to assess the efficacy and safety of the treatment for acute lymphoblastic leukemia Ph' positive adult patients with approved combinations of chemotherapy and tyrosine kinase inhibitor (TKI).
Efficay refers to the rate of Complete Molecular Response (BCR::ABL1/ABL1 ratio 0.01%) in eah treatment arm. Safety refers to measurement of i) Adverse events (AEs) and serious adverse events (SAEs) according to standard clinical and laboratory tests (hematology and chemistry, physical examination, vital sign measurements, and diagnostic tests), ii) incidence and degree of cytopenias and iii) incidence and degree of infections.
Low-dose chemotherapy will be given together with the TKI imatinib to patients of all ages as induction to remission phase.
Consolidation treatment will continue with low-dose chemotherapy with imatinib if the patient fullfills both criteria: to show a measurable residual disease (MRD) value lower than 0,01% at 3 month of therapy, and not showing IKZF1plus genetics Those patients have any of these 2 conditions will be considered high-risk patients and will recieve consolidation treatment intensification with low-dose chemotherapy plus ponatinib as TKI and allogeneic stem cell transplantation (allo SCT). The remaining patients (standard-risk) will receive maintenance chemotherapy together with imatinib or ponatinib and will not be submitted to alloSCT.
Detailed description
The goal of this prospective, multicenter, open observational study is to assess the efficacy and safety of the treatment for acute lymphoblastic leukemia Ph' positive adult patients with approved combinations of chemotherapy and tyrosine kinase inhibitor (TKI).
Efficay refers to the rate of Complete Molecular Response (BCR::ABL1/ABL1 ratio 0.01%) in each treatment arm. Safety refers to measurement of i) Adverse events (AEs) and serious adverse events (SAEs) according to standard clinical and laboratory tests (hematology and chemistry, physical examination, vital sign measurements, and diagnostic tests), ii) incidence and degree of cytopenias and iii) incidence and degree of infections.
Low-dose chemotherapy induction phase with vincristine (dose 1.5 mg/m2 at days 1, 8, 15 and 22), dexamethasone (dose 40 mg days 1-2, 8-9,15-16 and 22-23) will be given together with the TKI imatinib (dose 600 mg from day to consolidation start) to all patients of all ages as induction to remission phase.
Consolidation treatment will continue with low-dose chemotherapy with methotrexate (dose 1000 mg/m2 on day 1 with 24h infusion) and arabinoside of cytarabine (dose 1000 mg/m2/ days 1, 3 and 5 with 2h infusion) with imatinib (dose 600 mg per day) if the patient fullfills both criteria: i) to show a measurable residual disease (MRD) value <0,01% at 3 month of therapy, and ii) not showing IKZF1plus genetics.
Those patients having any of these 2 conditions will be considered high-risk patients and will recieve consolidation treatment intensification with low-dose chemotherapy (same as described above) plus ponatinib (dose 30 mg per day) as TKI and allogeneic stem cell transplantation (alloSCT) followed by maintenance chemotherapy with mercaptopurine (dose 50 mg/m2 on days 1 to 28) and methotrexate (dose 20 mg/m2 on days 1, 8, 15 and 22) together with imatinib (dose 600 mg per day) or ponatinib (15 mg per day) up to 5 years. The remaining patients (standard-risk) will receive maintenance chemotherapy (as described above) together with imatinib (dose 600 mg per day) or ponatinib (15 mg per day) up to 5 years and will not be submitted to alloSCT.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Complete molecular response and low risk genetics | – | Drug: Vincristine, Drug: Dexamethasone, Drug: Imatinib, Drug: Cytarabine, Drug: Mercaptopurine, Drug: MethotrexatePatients in Complete Remission and Complete Molecular Response at end Induction therapy will receive consolidation with imatinib (or dasatinib if intolerance) and chemotherapy, unless they show the IKZF1plus genotype, which will imply switch to the not complete molecular response or high-risk genetics (IKZ1plus) group. |
| Not complete molecular response or high-risk genetics (IKZF1plus) | – | Drug: Vincristine, Drug: Dexamethasone, Drug: Imatinib, Drug: Cytarabine, Drug: Mercaptopurine, Drug: Methotrexate, Drug: Ponatinib, Procedure: allogeneic stem cell transplantation, Procedure: Total body irradiation, Drug: Cyclophosphamide, Drug: FludarabinePatients in Complete Remission and without Complete Molecular Response at the end of Induction therapy or showing the IKZF1plus genotype, will receive consolidation treatment with ponatinib and chemotherapy followed by allogeneic stem cell transplantation and maintenance therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults aged 18 or over years with newly diagnosed Ph-positive or BCR::ABL1-positive acute lymphoblastic leukemia (Ph+ ALL).
Key inclusion criteria (4 listed)
- Patients with de novo avute lymphoblastic leukeima (ALL) Philadelphia chromosome-positive (BCR::ABL1) aged ≥18 years.
- CML blast crisis will be included. These patients will always receive transplantation, regardless of the molecular response or the genetic risk, following the recommendations of the SEHH CML group (Chronic Myleoid Leukemia Group from the Spanish Society of Hematology).
- Performance status 0-2; patients with performance status>2 attributable to ALL can be included.
- Patients without functional alteration of organs; liver function: total bilirubin, GOT, GPT, GGT and alkaline phosphatase less than 3 times the upper limit of the normal range of the laboratory; renal function: serum creatinine <2 mg/dl or creatinine clearance > 30 ml/min (except altered renal function attributable to ALL); normal heart function: EF ventricular > 50%; absence of severe chronic respiratory disease. In case that the alterations are secondary to the disease, it is at the discretion of the physician to determine if the patient can be included in the study.
Key exclusion criteria (10 listed)
- Any other subtype of ALL.
- Patients with chronic liver disease.
- Patients with chronic respiratory failure.
- Renal failure not due to ALL.
- Lipase and amylase>1.5× ULN.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vincristinedose 1.5 mg/m2 at days 1, 8, 15 and 22 | Drug | Complete molecular response and low risk genetics, Not complete molecular response or high-risk genetics (IKZF1plus) |
| Dexamethasone40 mg on days 1-2, 8-9,15-16 and 22-23 | Drug | Complete molecular response and low risk genetics, Not complete molecular response or high-risk genetics (IKZF1plus) |
| Imatinib600 mg per day from 1 to up to 5 years | Drug | Complete molecular response and low risk genetics, Not complete molecular response or high-risk genetics (IKZF1plus) |
| Cytarabine1000 mg/m2/ on days 1, 3 and 5 of consolidation with 2h infusion | Drug | Complete molecular response and low risk genetics, Not complete molecular response or high-risk genetics (IKZF1plus) |
| Mercaptopurine50 mg/m2 on days 1 to 28 of maintenance | Drug | Complete molecular response and low risk genetics, Not complete molecular response or high-risk genetics (IKZF1plus) |
| Methotrexate1000 mg/m2 on day 1 of consolidation with 24h infusion; and 20 mg/m2 on days 1, 8, 15 and 22 of maintenance | Drug | Complete molecular response and low risk genetics, Not complete molecular response or high-risk genetics (IKZF1plus) |
| Ponatinib15 mg per day from consolidation start up to 5 years | Drug | Not complete molecular response or high-risk genetics (IKZF1plus) |
| allogeneic stem cell transplantationAllogeneic stem cell transplantation from hematpoietic stem cells progenitors of familiar or not familiar origin. Cord blood transplantation can also be done. | Procedure or surgery | Not complete molecular response or high-risk genetics (IKZF1plus) |
| Total body irradiationFractionated dose with total dose of 12 Gy between days -4 and -1 of allogeneic stem cell transplantation (alloSCT) | Procedure or surgery | Not complete molecular response or high-risk genetics (IKZF1plus) |
| Cyclophosphamide60 mg/kg on days -6 and -5 before alloSCT | Drug | Not complete molecular response or high-risk genetics (IKZF1plus) |
| Fludarabine30 mg/m2 intravenous on days -7, -6, -5 y -4 before alloSCT (alternative to cyclophosphamide) | Drug | Not complete molecular response or high-risk genetics (IKZF1plus) |
Primary outcome
Overall survival
Time frame: 5 Years
Improvement of OS compared to that observed in the previous protocols (PETHEMA LALPh08 and LALOPh07).
5 secondary outcomes
Change the complete molecular response (CMR) rate with Ponatinib
Time frame: 5 Years
Limit the number of alloTPH compared to that observed in the previous protocols (PETHEMA LALPh08 and LALOPh07).
Time frame: 5 Years
Maintenance
Time frame: 5 Years
Treatment with TKI after HSCT
Time frame: 5 Years
Assess the frequency and degree of Adverse Events
Time frame: 5 Years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2023.
- Background: PubMed 23716539Chiaretti S, Vitale A, Cazzaniga G, Orlando SM, Silvestri D, Fazi P, Valsecchi MG, Elia L, Testi AM, Mancini F, Conter V, te Kronnie G, Ferrara F, Di Raimondo F, Tedeschi A, Fioritoni G, Fabbiano F, Meloni G, Specchia G, Pizzolo G, Mandelli F, Guarini A, Basso G, Biondi A, Foa R. Clinico-biological features of 5202 patients with acute lymphoblastic leukemia enrolled in the Italian AIEOP and GIMEMA protocols and stratified in age cohorts. Haematologica. 2013 Nov;98(11):1702-10. doi: 10.3324/haematol.2012.080432. Epub 2013 May 28.
- Background: PubMed 24277073Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. doi: 10.1182/blood-2013-09-529008. Epub 2013 Nov 25.
- Background: PubMed 19797728Ribera JM, Oriol A, Gonzalez M, Vidriales B, Brunet S, Esteve J, Del Potro E, Rivas C, Moreno MJ, Tormo M, Martin-Reina V, Sarra J, Parody R, de Oteyza JP, Bureo E, Bernal MT; Programa Espanol de Tratamiento en Hematologia; Grupo Espanol de Trasplante Hemopoyetico Groups. Concurrent intensive chemotherapy and imatinib before and after stem cell transplantation in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Final results of the CSTIBES02 trial. Haematologica. 2010 Jan;95(1):87-95. doi: 10.3324/haematol.2009.011221. Epub 2009 Oct 1.
- Background: PubMed 25682595Daver N, Thomas D, Ravandi F, Cortes J, Garris R, Jabbour E, Garcia-Manero G, Borthakur G, Kadia T, Rytting M, Konopleva M, Kantarjian H, O'Brien S. Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica. 2015 May;100(5):653-61. doi: 10.3324/haematol.2014.118588. Epub 2015 Feb 14.
- Background: PubMed 27515250Chiaretti S, Vitale A, Vignetti M, Piciocchi A, Fazi P, Elia L, Falini B, Ronco F, Ferrara F, De Fabritiis P, Luppi M, La Nasa G, Tedeschi A, Califano C, Fanin R, Dore F, Mandelli F, Meloni G, Foa R. A sequential approach with imatinib, chemotherapy and transplant for adult Ph+ acute lymphoblastic leukemia: final results of the GIMEMA LAL 0904 study. Haematologica. 2016 Dec;101(12):1544-1552. doi: 10.3324/haematol.2016.144535. Epub 2016 Aug 11.
- Background: PubMed 25878120Chalandon Y, Thomas X, Hayette S, Cayuela JM, Abbal C, Huguet F, Raffoux E, Leguay T, Rousselot P, Lepretre S, Escoffre-Barbe M, Maury S, Berthon C, Tavernier E, Lambert JF, Lafage-Pochitaloff M, Lheritier V, Chevret S, Ifrah N, Dombret H; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia. Blood. 2015 Jun 11;125(24):3711-9. doi: 10.1182/blood-2015-02-627935. Epub 2015 Apr 15.
- Background: PubMed 21931113Foa R, Vitale A, Vignetti M, Meloni G, Guarini A, De Propris MS, Elia L, Paoloni F, Fazi P, Cimino G, Nobile F, Ferrara F, Castagnola C, Sica S, Leoni P, Zuffa E, Fozza C, Luppi M, Candoni A, Iacobucci I, Soverini S, Mandelli F, Martinelli G, Baccarani M; GIMEMA Acute Leukemia Working Party. Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2011 Dec 15;118(25):6521-8. doi: 10.1182/blood-2011-05-351403. Epub 2011 Sep 19.
- Background: PubMed 29046900Ravandi F, Othus M, O'Brien SM, Forman SJ, Ha CS, Wong JYC, Tallman MS, Paietta E, Racevskis J, Uy GL, Horowitz M, Takebe N, Little R, Borate U, Kebriaei P, Kingsbury L, Kantarjian HM, Radich JP, Erba HP, Appelbaum FR. US Intergroup Study of Chemotherapy Plus Dasatinib and Allogeneic Stem Cell Transplant in Philadelphia Chromosome Positive ALL. Blood Adv. 2016 Dec 27;1(3):250-259. doi: 10.1182/bloodadvances.2016001495.
- Background: PubMed 34516628Sugiura I, Doki N, Hata T, Cho R, Ito T, Suehiro Y, Tanaka M, Kako S, Matsuda M, Yokoyama H, Ishikawa Y, Taniguchi Y, Hagihara M, Ozawa Y, Ueda Y, Hirano D, Sakura T, Tsuji M, Kamae T, Fujita H, Hiramoto N, Onoda M, Fujisawa S, Hatta Y, Dobashi N, Nishiwaki S, Atsuta Y, Kobayashi Y, Hayakawa F, Ohtake S, Naoe T, Miyazaki Y. Dasatinib-based 2-step induction for adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood Adv. 2022 Jan 25;6(2):624-636. doi: 10.1182/bloodadvances.2021004607.
- Background: PubMed 26065651Kim DY, Joo YD, Lim SN, Kim SD, Lee JH, Lee JH, Kim DH, Kim K, Jung CW, Kim I, Yoon SS, Park S, Ahn JS, Yang DH, Lee JJ, Lee HS, Kim YS, Mun YC, Kim H, Park JH, Moon JH, Sohn SK, Lee SM, Lee WS, Kim KH, Won JH, Hyun MS, Park J, Lee JH, Shin HJ, Chung JS, Lee H, Eom HS, Lee GW, Cho YU, Jang S, Park CJ, Chi HS, Lee KH; Adult Acute Lymphoblastic Leukemia Working Party of the Korean Society of Hematology. Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Blood. 2015 Aug 6;126(6):746-56. doi: 10.1182/blood-2015-03-636548. Epub 2015 Jun 11.
- Background: PubMed 33991360Jain N, Maiti A, Ravandi F, Konopleva M, Daver N, Kadia T, Pemmaraju N, Short N, Kebriaei P, Ning J, Cortes J, Jabbour E, Kantarjian H. Inotuzumab ozogamicin with bosutinib for relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia or lymphoid blast phase of chronic myeloid leukemia. Am J Hematol. 2021 Aug 1;96(8):1000-1007. doi: 10.1002/ajh.26238. Epub 2021 May 28.
- Background: PubMed 17213285Vignetti M, Fazi P, Cimino G, Martinelli G, Di Raimondo F, Ferrara F, Meloni G, Ambrosetti A, Quarta G, Pagano L, Rege-Cambrin G, Elia L, Bertieri R, Annino L, Foa R, Baccarani M, Mandelli F. Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive patients with acute lymphoblastic leukemia without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) LAL0201-B protocol. Blood. 2007 May 1;109(9):3676-8. doi: 10.1182/blood-2006-10-052746. Epub 2007 Jan 9.
- Web page of the sponsor of the studyLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Josep M Ribera Santasusana, MD principal investigator
Institut Catala d'Oncologia-Hospital Universitari Germans Trias i Pujol
Questions about this trial
What is this clinical trial studying?
An observational study of Lymphoblastic Leukemia and Philadelphia-Positive ALL, run by PETHEMA Foundation.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 19 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Josep M Ribera Santasusana, MD (0034934978387, jribera@iconcologia.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: 5 Years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06175702, which also lists 33 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2023.